[unreadable] Leptomeningeal carcinomatosis (LMC), a state of metastatic tumor invasion of the cerebrospinal fluid (CSF) space, carries a poor prognosis with short survival averaging 2-4 months. Currently the diagnosis of LMC is based on cytology demonstration of unequivalent malignant cells. Unfortunately, this is accomplished only after advanced CSF invasion has already taken place. Cytology evaluation at earlier stages of LMC is invariably indeterminate or false negative. We hypothesize that the definitive diagnosis of LMC can be accomplished using molecular pathology criteria significantly prior to current cytologic definitive diagnosis. The molecular pathology criteria will be facilitated through the use of topographic genotyping (TG), a patented platform for integrated analysis exclusively owned and commercialized by RedPath Integrated Pathology. Under TG, microdissected cytology cells and the free DNA in the CSF will be analyzed for the presence, cumulative amount and timing of mutational damage leading to earlier and more definitive diagnosis of cancer superior to that based on microscopic examination alone. Quality control measures will also be innovated for clinical application and the analytical and clinical precision of the technique will be characterized. Specific aims for Phase 1 are 1) to apply TG to the CSF from patients with and without LMC in order to define objective molecular pathology criteria constituting malignant involvement, 2) to compare the efficacy of TG detection of LMC to traditional cytologic diagnosis in turn defining the sensitivity, specificity and predictive value of molecular pathology detection and 3) to define the cumulative amount of acquired mutational damage and time course of specific mutation acquisition (dynamic mutational profile) of primary, visceral metastatic and leptomeningeal tumor to better understand the timing and mechanisms underlying CNS involvement in LMC. The results of this study will greatly impact the current practice of pathology and cancer diagnosis by incorporating molecular analysis into routine pathology evaluation for more definitive and objective diagnosis of cancer. Further, the advantage of earlier detection can significantly improve the effectiveness of medical therapy of this increasingly common complication of visceral cancer with measurable benefits to patients both in survival and quality of life. [unreadable] [unreadable]